A Sluggish Guy's Way To The Cisplatin Triumph
.. The proteins involved in cell rescue, defense, and virulence confer protection to the cell and assure survival upon various stresses. Molecular chaperones are very conserved and has the function related to maintenance of conformational equilibrium of proteins (Hartl, 1996). In this study, as could be expected, were identified stress-related proteins regulated in the presence of argentilactone (Tables ?(Tables1,1, ?,2).2). In addition to the heat shock proteins, proteasome component C5 and sulfur metabolite repression control protein C were exclusive to P. lutzii exposed to argentilactone. This result could indicate the involvement of these proteins in protecting the fungus from the stress generated by argentilactone. Our proteomic analyses indicate a global reorganization of P. lutzii carbohydrate metabolism during the exposure to argentilactone. One change detected here is the decrease of several enzymes of glycolytic pathway such as enolase, phosphoglucomutase, phosphoglycerate kinase, pyruvate kinase, and those exclusive to the absence of argentilactone as glucokinase and phosphofructokinase (Table ?(Table2).2). The down-regulation of succinate dehydrogenase, two malate dehydrogenases, and isocitrate ERK inhibitor in vitro dehydrogenase subunits 1 and 2 (Table ?(Table2),2), shows that Krebs cycle is not completely functioning in P. lutzii. In the presence of argentilactone, P. lutzii decreased the glucose consume (Figure ?(Figure5),5), suggesting that glycolysis is partially blocked. In addition, the gluconeogenesis is also not completely functioning, as phosphoenolpyruvate carboxykinase is less abundant (Table ?(Table2).2). Phosphoenolpyruvate carboxykinase plays an importantl role in the pathogenesis of tuberculosis, sinceit is essential for Mycobacterium tuberculosis during mouse infection. M. tuberculosis utilizes primarily gluconeogenic substrates for in vivo persistence, suggesting that this enzyme represents a target for treatments (Marrero et al., 2010). Figure 5 Glucose quantification. The level of glucose was quantified by enzymatic kit after 0, 2, 4, 6, 8, 10, 12 and 24 h. The control was performed with cells in the absence of argentilactone. The Student's t-test was used for statistical comparisons, and the ... The glyoxylate cycle is not completely functioning in the presence of argentilactone as the enzyme isocitrate lyase is less abundant (Table ?(Table2).2). This finding is consistent with our previous results showing that the P. lutzii isocitrate lyase recombinant and native forms were inhibited in the presence of argentilactone (Prado et al., 2014). On the other hand, malate synthase is more abundant. Under the absence of six-carbon elements, the glyoxylate cycle is induced (Fernandez et al., 1993). The glyoxylate pathway is important in the generations of C4 dicarboxylic acids from acetyl-CoA units, bypassing the decarboxylation steps in the TCA cycle. The cycle is important to fungal pathogenesis.